An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells

TLDR

The aryl hydrocarbon receptor (AHR) is known to mediate immunosuppression after dioxin binding and has recently been implicated in directing T cell differentiation toward regulatory T cells versus Th17 cells. This study aims to show that kynurenine activates AHR and to examine how TGF‑β dependence on AHR influences optimal regulatory T cell generation. Using mouse tissues and cells, the authors investigated kynurenine‑induced AHR activation and the role of TGF‑β in upregulating AHR for Treg differentiation. They found that kynurenine‑activated AHR drives Treg generation, linking IDO activity to Treg production and underscoring AHR’s central role in T cell fate decisions.

Abstract

The aryl hydrocarbon receptor (AHR) has been known to cause immunosuppression after binding dioxin. It has recently been discovered that the receptor may be central to T cell differentiation into FoxP3(+) regulatory T cells (Tregs) versus Th17 cells. In this paper, we demonstrate that kynurenine, the first breakdown product in the IDO-dependent tryptophan degradation pathway, activates the AHR. We furthermore show that this activation leads to AHR-dependent Treg generation. We additionally investigate the dependence of TGF-beta on the AHR for optimal Treg generation, which may be secondary to the upregulation of this receptor that is seen in T cells postexposure to TGF-beta. These results shed light on the relationship of IDO to the generation of Tregs, in addition to highlighting the central importance of the AHR in T cell differentiation. All tissues and cells were derived from mice.